Peroxiredoxin 4 Inhibits Il-1 Beta-Induced Chondrocyte Apoptosis Via Pi3k/Akt Signaling

Background: Chondrocytes apoptosis induced by reactive oxygen species (ROS) plays a critical role in the pathogenesis of osteoarthritis (OA). Peroxiredoxin 4 (PRDX4), a member of the PRDX family, is essential for removing metabolic free radicals and reducing intracellular ROS. In this study, we sought to investigate the roles of PRDX4 on interleukin 1 beta (IL-1 beta)-induced chondrocyte apoptosis.Methods: Primary chondrocytes were isolated from the articular cartilage of Sprague-Dawley rats, infected with PRDX4 overexpressing lentivirus and treated with IL-1 beta (10 ng/mL). Cell apoptosis and ROS production identified by flow cytometry. Protein expression levels was evaluated by Western blotting analysis. Nitric oxide (NO) production and Caspase-3/9 activation were assessed by the Griess reaction method and colorimetric assay kit, respectively.Results: PRDX4 overexpression in chondrocytes significantly decreased IL-1 beta-induced apoptosis. It also reversed the activity of IL-1 beta that increased ROS and NO production. PRDX4 overexpression reversed the activity of IL-1 beta that reduced the levels of Bcl-2, p-AKT and p-PRAS40, as well as increased Bax levels and Caspase-3/9 activation. More importantly, pre-treated with AKT inhibitor (AZD5363) significantly reduced the protective effects of PRDX4.Conclusions: Our data demonstrated that the regulatory effects of PRDX4 on IL-1 beta-induced chondrocyte apoptosis can be partially attributed to phosphatidylinositol 3-kinase/AKT signaling. These results indicate that PRDX4 might play a protective role in OA cartilage degeneration. (C) 2017 Elsevier Masson SAS. All rights reserved.